{"doi":"10.1172/jci137712","title":"Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function","abstract":"Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function.","journal":"Journal of Clinical Investigation","year":2020,"id":55834,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":90,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289274,"name":"Luisa Morales‐Nebreda","orcid":"0000-0002-7126-0518","position":1,"is_corresponding":false},{"id":289275,"name":"Manuel A. Torres Acosta","orcid":"0000-0002-9939-7401","position":2,"is_corresponding":false},{"id":289276,"name":"Kishore R. Anekalla","orcid":"0000-0002-8366-5782","position":3,"is_corresponding":false},{"id":289277,"name":"Shang-Yang Chen","orcid":"0000-0002-6864-4713","position":4,"is_corresponding":false},{"id":232815,"name":"Hiam Abdala‐Valencia","orcid":"0000-0003-3384-5299","position":5,"is_corresponding":false},{"id":232814,"name":"Yuliya Politanska","orcid":"0000-0002-6766-988X","position":6,"is_corresponding":false},{"id":269569,"name":"Paul Cheresh","orcid":null,"position":7,"is_corresponding":false},{"id":289278,"name":"Mahzad Akbarpour","orcid":"0000-0001-9260-1716","position":8,"is_corresponding":false},{"id":230872,"name":"Elizabeth M. Steinert","orcid":"0000-0002-6947-2271","position":9,"is_corresponding":false},{"id":230870,"name":"Samuel E. Weinberg","orcid":"0000-0002-9532-7051","position":10,"is_corresponding":false},{"id":267595,"name":"Benjamin D. Singer","orcid":"0000-0001-5775-8427","position":11,"is_corresponding":false},{"id":267590,"name":"Kathryn A. Helmin","orcid":"0009-0006-8857-9943","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T21:05:29.672878Z","pmid":"32897881","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}